tbuckley/cabot-search huggingface dataset:
Effect of once-per-day tacrolimus versus twice-per-day ciclosporin on 3-year incidence of chronic lung allograft dysfunction after lung transplantation in Scandinavia (ScanCLAD): a multicentre randomised controlled trial
Authors: Göran Dellgren, Thomas Kromann Lund, Peter Raivio, Inga Leuckfeld, Johan Svahn, Erik C Holmberg, Peter Skov Olsen, Maija Halme, Arnt Fiane, Sandra Lindstedt, Gerdt C Riise, Jesper Magnusson
Journal: The Lancet Respiratory Medicine (2023)
The ERS PROFILE.net Clinical Research Collaboration is dedicated to the set-up of an academic network to enhance imaging-based management of progressive pulmonary fibrosis
Authors: Julien Guiot, Simon L.F. Walsh
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>AI has the potential to revolutionise the way we diagnose and treat patients suffering from fibrotic ILDs. HRCT analysis and abnormalities quantification can facilitate diagnosis and monitoring of treatment response to assist clinicians.</b>https://bit.ly/3rKI2Iq
Aldosterone Synthase Inhibition With Lorundrostat for Uncontrolled Hypertension
Authors: Luke J. Laffin, David Rodman, James M. Luther, Anand Vaidya, Matthew R. Weir, Natasa Rajicic, B. T. Slingsby, Steven E. Nissen, Richard Beasley, Matthew Budoff, George Carr, Michael Carroll, Jose Cevallos Yepez, Anil Chhabra, Frank Cole, Leonard Dunn, William Eaves, Valentine Ebuh, Roger Estevez, Glenn Gould, Matthew Hong, Bruce Iteld, Mahendra Jain, Charles Kemp, Christina Kennelly, Mark Kleiner, Mark Kutner, Luke Laffin, Joseph Lambert, Gilbert Ledesma, Keung Lee, John Lentz, Steven Lupovitch,  James Luther, Lon Lynn, Obadias Marquez, Mobeen Mazhar, David Morin, Joel Neutel, Yaa Oppong, Merlin Osorio, Andres Patron, Walter Pharr, Mercedes Ponce de Leon, Lilia Rodriguez-Ables, Jeffrey Rosen, Issac Sachmechi, Ronald Surowitz, Larkin Wadsworth, Jeffrey Wayne, Zahid Zafar
Journal: JAMA (2023)

Excess aldosterone production contributes to hypertension in both classical hyperaldosteronism and obesity-associated hypertension. Therapies that reduce aldosterone synthesis may lower blood pressure.
SEMA3B‐AS1 suppresses colorectal carcinoma progression by inhibiting Semaphorin 3B‐dependent VEGF signaling pathway activation
Authors: Yi‐Qing Wang, Hui Chen, Shuang Xu, Cong‐Rui Liao, Anran Xu, Yue Han, Min‐Hui Yang, Li Zhao, Sha‐Sha Hu, Lan Wang, Qing‐Yuan Li, Ling‐Ying Zhan, Yan‐Qing Ding, Shuang Wang
Journal: MedComm (2023)

Abstract Mounting evidence has demonstrated the considerable regulatory effects of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of various carcinomas. LncRNA Semaphorin 3B (SEMA3B) antisense RNA 1 ( SEMA3B‐AS1 ) has been found to be dysregulated in a few carcinomas recently. However, its potential function and mechanism in colorectal carcinoma (CRC) have not yet been examined. Here we show that SEMA3B‐AS1 acts as a crucial regulator of CRC progression. We found that SEMA3B‐AS1 expression was downregulated in CRC cell lines and tissues. Downregulation of SEMA3B‐AS1 was significantly associated with poor survival in CRC patients. Overexpression of SEMA3B‐AS1 reduced the cell growth and metastasis of CRC in vivo and in vitro. In addition, SEMA3B‐AS1 promoted the expression of its sense‐cognate gene SEMA3B, a member of the Semaphorin family (SEMAs), by recruiting EP300 to induce H3K9 acetylation at the SEMA3B promoter. Furthermore, we proved that SEMA3B‐AS1 suppressed CRC angiogenesis by affecting the vascular endothelial growth factor signaling pathway activation which was regulated by the SEMA3B‐NRP1 axis. Our work unravels a novel mechanism of SEMA3B‐AS1 in the inhibition of CRC malignant progression and highlights its probability as a new promising diagnostic marker and therapeutic target for CRC interventions.
Pre-screening for non-diagnostic coronary computed tomography angiography
Authors: Ramtin Hakimjavadi, Juan Lu, Yeung Yam, Girish Dwivedi, Gary R Small, Benjamin J W Chow
Journal:  (2023)

Abstract Aims Indiscriminate coronary computed tomography angiography (CCTA) referrals for suspected coronary artery disease could result in a higher rate of equivocal and non-diagnostic studies, leading to inappropriate downstream resource utilization or delayed time to diagnosis. We sought to develop a simple clinical tool for predicting the likelihood of a non-diagnostic CCTA to help identify patients who might be better served with a different test. Methods and results We developed a clinical scoring system from a cohort of 21 492 consecutive patients who underwent CCTA between February 2006 and May 2021. Coronary computed tomography angiography study results were categorized as normal, abnormal, or non-diagnostic. Multivariable logistic regression analysis was conducted to produce a model that predicted the likelihood of a non-diagnostic test. Machine learning (ML) models were utilized to validate the predictor selection and prediction performance. Both logistic regression and ML models achieved fair discriminate ability with an area under the curve of 0.630 [95% confidence interval (CI) 0.618–0.641] and 0.634 (95% CI 0.612–0.656), respectively. The presence of a cardiac implant and weight &amp;gt;100 kg were among the most influential predictors of a non-diagnostic study. Conclusion We developed a model that could be implemented at the ‘point-of-scheduling’ to identify patients who would be best served by another non-invasive diagnostic test.
Cysteine Enrichment Mediates Co-Option of Uricase in Reptilian Skin and Transition to Uricotelism
Authors: Giulia Mori, Anastasia Liuzzi, Luca Ronda, Michele Di Palma, Magda S Chegkazi, Soi Bui, Mitla Garcia-Maya, Jasmine Ragazzini, Marco Malatesta, Emanuele Della Monica, Claudio Rivetti, Parker B Antin, Stefano Bettati, Roberto A Steiner, Riccardo Percudani
Journal: Molecular Biology and Evolution (2023)

Uric acid is the main means of nitrogen excretion in uricotelic vertebrates (birds and reptiles) and the end product of purine catabolism in humans and a few other mammals. While uricase is inactivated in mammals unable to degrade urate, the presence of orthologous genes without inactivating mutations in avian and reptilian genomes is unexplained. Here we show that the Gallus gallus gene we name cysteine-rich urate oxidase (CRUOX) encodes a functional protein representing a unique case of cysteine enrichment in the evolution of vertebrate orthologous genes. CRUOX retains the ability to catalyze urate oxidation to hydrogen peroxide and 5-hydroxyisourate (HIU), albeit with a 100-fold reduced efficiency. However, differently from all uricases hitherto characterized, it can also facilitate urate regeneration from HIU, a catalytic property that we propose depends on its enrichment in cysteine residues. X-ray structural analysis highlights differences in the active site compared to known orthologs and suggests a mechanism for cysteine-mediated self-aggregation under H2O2-oxidative conditions. Cysteine enrichment was concurrent with the transition to uricotelism and a shift in gene expression from the liver to the skin where CRUOX is co-expressed with β-keratins. Therefore, the loss of urate degradation in amniotes has followed opposite evolutionary trajectories: while uricase has been eliminated by pseudogenization in some mammals, it has been repurposed as a redox-sensitive enzyme in the reptilian skin.
Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells
Authors: Md Moniruzzaman, M. Arifur Rahman, Ran Wang, Kuan Yau Wong, Alice C.-H. Chen, Alexandra Mueller, Steven Taylor, Alexa Harding, Thishan Illankoon, Percival Wiid, Haressh Sajiir, Veronika Schreiber, Lucy D. Burr, Michael A. McGuckin, Simon Phipps, Sumaira Z. Hasnain
Journal: The Journal of Experimental Medicine (2023)

Major histocompatibility complex (MHC) II is dynamically expressed on mucosal epithelial cells and is induced in response to inflammation and parasitic infections, upon exposure to microbiota, and is increased in chronic inflammatory diseases. However, the regulation of epithelial cell-specific MHC II during homeostasis is yet to be explored. We discovered a novel role for IL-22 in suppressing epithelial cell MHC II partially via the regulation of endoplasmic reticulum (ER) stress, using animals lacking the interleukin-22-receptor (IL-22RA1), primary human and murine intestinal and respiratory organoids, and murine models of respiratory virus infection or with intestinal epithelial cell defects. IL-22 directly downregulated interferon-γ-induced MHC II on primary epithelial cells by modulating the expression of MHC II antigen A α (H2-Aα) and Class II transactivator (Ciita), a master regulator of MHC II gene expression. IL-22RA1-knockouts have significantly higher MHC II expression on mucosal epithelial cells. Thus, while IL-22-based therapeutics improve pathology in chronic disease, their use may increase susceptibility to viral infections.
IL-22: Immunity’s bittersweet symphony
Authors: Jinzhi Duan, Juan D. Matute, Richard S. Blumberg
Journal: The Journal of Experimental Medicine (2023)

Epithelial cells play a crucial role in barrier defense. Here, Moniruzzaman et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20230106) discovered that interleukin-22 (IL-22) represses MHC class II expression by epithelial cells with an opposite impact on chronic inflammatory disease and viral infection.
Error in Figure 2
Journal: JAMA Pediatrics (2023)

Jeanie L. Y. Cheong, MD; Joy E. Olsen, PhD; Katherine J. Lee, PhD; Alicia J. Spittle, PhD; Gillian F. Opie, MBBS; Marissa Clark, MBBS; Rosemarie A. Boland, PhD; Gehan Roberts, PhD; Elisha K. Josev, PhD; Noni Davis, MBBS; Leah M. Hickey, MD; Peter J. Anderson, PhD; Lex W. Doyle, MD; Victorian Infant Collaborative Study Group; Jeanie Cheong; Peter Anderson; Merilyn Bear; Rosemarie Boland; Alice Burnett; Margaret Charlton; Marissa Clark; Janet Courtot; Noni Davis; Lex Doyle; Julianne Duff; Rachel Ellis; Anjali Haikerwal; Leah Hickey; Marie Hayes; Elisha Josev; Elaine Kelly; Katherine Lee; Marion McDonald; Bronwyn Novella; Joy Olsen; Gillian Opie; Gehan Roberts; Katherine Scott; Alicia Spittle; Penelope Stevens; Anne-Marie Turner
GWASs and polygenic scores inherit all the old problems of heritability estimates
Authors: Sahotra Sarkar
Journal: Behavioral and Brain Sciences (2023)

Abstract Polygenic score (PGS) computations assume an additive model of gene action because associations between phenotypes and alleles at different loci are compounded, ignoring interactions between alleles or loci let alone between genotype and environment. Consequently, PGSs are subject to the same objections that invalidated traditional heritability analyses in the 1970s. Thus, PGSs should not be used in the social sciences.
Complex interactions confound any unitary approach to social phenomena, not just biological ones
Authors: Darren Burke
Journal: Behavioral and Brain Sciences (2023)

Abstract Although Burt clearly explains how modern genomic techniques work, and describes their limitations, her conclusion that they are therefore not valuable additions to understanding social outcomes is unwarranted. Understanding the causes of complex social outcomes depends on understanding how social, individual, and genetic factors complexly interact with each other. None can be understood without reference to the others.
Polygenic scores and social science
Authors: Walter Veit, Heather Browning
Journal: Behavioral and Brain Sciences (2023)

Abstract It is a hotly contested issue whether polygenic scores should play a major role in the social sciences. Here, we defend a methodologically pluralist stance in which sociogenomics should abandon its hype and recognize that it suffers from all the methodological difficulties of the social sciences, yet nevertheless maintain an optimistic stance toward a more cautious use.
Drowning in shallow causality
Authors: Hao Shen, Marcus W. Feldman
Journal: Behavioral and Brain Sciences (2023)

It has been known for decades that inference concerning genetic causes of human behavioral phenotypes cannot be legitimately made from correlations among relatives. We claim that these inferential difficulties cannot be overcome by assigning different names to causes inferred from within-family and population-level genome-wide association studies (GWASs). For educational attainment, for example, unraveling gene-environment interactions requires more than new names for causes.
Polygenic scores, and the genome-wide association studies they derive from, will have difficulty identifying genes that predispose one to develop a social behavioral trait
Authors: Edward Fox
Journal: Behavioral and Brain Sciences (2023)

Abstract Polygenic scores (PGSs) have several limitations. They are confounded with environmental effects on behavior and cannot be used to study how mutations affect brain function and behavior. For this, mutations with large effects, which often arise in only one geographical population are needed. Genome-wide association studies (GWASs), commonly used for identifying mutations, have difficulty detecting these mutations. A strategy that overcomes this challenge is discussed.
Beware of the phony horserace between genes and environments
Authors: Sam Trejo, Daphne Oluwaseun Martschenko
Journal: Behavioral and Brain Sciences (2023)

Abstract Although Burt provides a valuable critique of the scientific value of integrating genetic data into social science research, she reinforces rather than disrupts the age-old horserace between genetic effects and environmental effects. We must move past this false dichotomy to create a new ontology that recognizes the ways in which genetic and environmental processes are inextricably intertwined.
Theory matters for identifying a causal role for genetic factors in socioeconomic outcomes
Authors: Steven N. Durlauf, Aldo Rustichini
Journal: Behavioral and Brain Sciences (2023)

Abstract Any empirical claim about the role of genes in socioeconomic outcomes involves successfully addressing the identification problem. This commentary argues that socioeconomic outcomes such as education are sufficiently complex, involving so many mechanisms, that understanding the role genes requires the use of formal theoretical structures.
Shallow versus deep genetic causes
Authors: Adam C. Smith, Stephen M. Downes
Journal: Behavioral and Brain Sciences (2023)

Abstract We argue that Madole &amp; Harden's distinction between shallow versus deep genetic causes can bring some clarity to causal claims arising from genome-wide association studies (GWASs). However, the authors argue that GWAS only finds shallow genetic causes, making GWAS commensurate with the environmental studies they hope to supplant. We also assess whether their distinction applies best to explanations or causes.
Transposable Elements Are Co-opted as Oncogenic Regulatory Elements by Lineage-Specific Transcription Factors in Prostate Cancer
Authors: Giacomo Grillo, Tina Keshavarzian, Simon Linder, Christopher Arlidge, Lisanne Mout, Ankita Nand, Mona Teng, Aditi Qamra, Stanley Zhou, Ken J. Kron, Alex Murison, James R. Hawley, Michael Fraser, Theodorus H. van der Kwast, Ganesh V. Raj, Housheng Hansen He, Wilbert Zwart, Mathieu Lupien
Journal: Cancer Discovery (2023)

Abstract Transposable elements hold regulatory functions that impact cell fate determination by controlling gene expression. However, little is known about the transcriptional machinery engaged at transposable elements in pluripotent and mature versus oncogenic cell states. Through positional analysis over repetitive DNA sequences of H3K27ac chromatin immunoprecipitation sequencing data from 32 normal cell states, we report pluripotent/stem and mature cell state–specific “regulatory transposable elements.” Pluripotent/stem elements are binding sites for pluripotency factors (e.g., NANOG, SOX2, OCT4). Mature cell elements are docking sites for lineage-specific transcription factors, including AR and FOXA1 in prostate epithelium. Expanding the analysis to prostate tumors, we identify a subset of regulatory transposable elements shared with pluripotent/stem cells, including Tigger3a. Using chromatin editing technology, we show how such elements promote prostate cancer growth by regulating AR transcriptional activity. Collectively, our results suggest that oncogenesis arises from lineage-specific transcription factors hijacking pluripotent/stem cell regulatory transposable elements. Significance: We show that oncogenesis relies on co-opting transposable elements from pluripotent stem cells as regulatory elements altering the recruitment of lineage-specific transcription factors. We further discover how co-option is dependent on active chromatin states with important implications for developing treatment options against drivers of oncogenesis across the repetitive DNA. This article is featured in Selected Articles from This Issue, p. 2293
The challenges of sociogenomics make it more, not less, worthy of careful and innovative investigation
Authors: Matthew C. Keller
Journal: Behavioral and Brain Sciences (2023)

Abstract Influences on social traits involve a tangled interplay of genetic, social, and environmental factors. Moreover, there is increasing awareness that gene–environment correlations are real and potentially measurable. Such gene–environment correlations can mislead if they are uncontrolled and genetic associations are interpreted as being purely because of direct genetic effects. This complexity is cause for more and better investigation, not a reason to refrain from researching one of the potentially important factors (genetics) influencing trait variation.
Polygenic scores for social science: Clarification, consensus, and controversy
Authors: Callie H. Burt
Journal: Behavioral and Brain Sciences (2023)

Abstract In this response, I focus on clarifying my arguments, highlighting consensus, and addressing competing views about the utility of polygenic scores (PGSs) for social science. I also discuss an assortment of expansions to my arguments and suggest alternative approaches. I conclude by reiterating the need for caution and appropriate scientific skepticism.
Machine-Made Empathy? Why Medicine Still Needs Humans—Reply
Authors: John W. Ayers, Mark Dredze, Davey M. Smith
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Genetics can inform causation, but the concepts and language we use matters
Authors: Sara A. Hart, Christopher Schatschneider
Journal: Behavioral and Brain Sciences (2023)

Abstract Madole &amp; Harden describe how genetics can be used in a causal framework. We agree with many of their opinions but argue that comparing within-family designs to experiments is unnecessary and that the proposed influence of genetics on behavior can be better described as inus conditions.
On the big list of causes
Authors: Eric Turkheimer
Journal: Behavioral and Brain Sciences (2023)

Abstract The methodological shift from twin studies to genome-wide association studies (GWASs) diminished estimates of true genetic causation underlying statistical heritability of behavioral differences. The sum total of causal genetic influence on behavior is not zero, but, (a) no one cited in the target article ever thought this was the case, and (b) there is still little known about concrete instances of genetic causation.
Single-cell immune profiling of mouse liver aging reveals Cxcl2 + macrophages recruit neutrophils to aggravate liver injury
Authors: Yasong Liu, Jiaqi Xiao, Jianye Cai, Rong Li, Xin Sui, Jiebin Zhang, Tongyu Lu, Haitian Chen, Guihua Chen, Haibo Li, Chenhao Jiang, Xuegang Zhao, Cuicui Xiao, Yunguo Lei, Jia Yao, Guo Lv, Jinliang Liang, Yingcai Zhang, Jian-Rong Yang, Jun Zheng, Yang Yang
Journal: Hepatology (2023)

Background and Aims: Immune cells play a crucial role in liver aging. However, the impact of dynamic changes in the local immune microenvironment on age-related liver injury remains poorly understood. We aimed to characterize intrahepatic immune cells at different ages to investigate key mechanisms associated with liver aging. Approach and Results: We carried out single-cell RNA sequencing on mouse liver tissues at 4 different ages, namely, the newborn, suckling, young, and aged stages. The transcriptomic landscape, cellular classification, and intercellular communication were analyzed. We confirmed the findings by multiplex immunofluorescence staining, flow cytometry, in vitro functional experiments, and chimeric animal models. Nine subsets of 89,542 immune cells with unique properties were identified, of which Cxcl2 + macrophages within the monocyte/macrophage subset were preferentially enriched in the aged liver. Cxcl2 + macrophages presented a senescence-associated secretory phenotype and recruited neutrophils to the aged liver through the CXCL2-CXCR2 axis. Through the secretion of IL-1β and TNF-α, Cxcl2 + macrophages stimulated neutrophil extracellular traps formation. Targeting the CXCL2-CXCR2 axis limited the neutrophils migration toward the liver and attenuated age-related liver injury. Moreover, the relationship between Cxcl2 + macrophages and neutrophils in age-related liver injury was further validated by human liver transplantation samples. Conclusions: This in-depth study illustrates that the mechanism of Cxcl2 + macrophage-driven neutrophil activation involves the CXCL2-CXCR2 axis and provides a potential therapeutic strategy for age-related liver injury.
Decoding the Association Between Body Composition in Preterm Birth and Hypertension in Childhood
Authors: Amanda Casirati, Alberto Somaschini, Marco Somaschini
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal